We have been examining minimal deviation adrenocortical tumor cells in culture: the Y-1 strain, originally developed in Sato's laboratory in 1959. Originally we were only concerned with the transformation of Y-1 cells to more rapidly growing, non contact inhibited "mutants" which produced only low levels of steroids, had low levels of cyclic AMP and were insensitive to the nucleotide. In the first year of this project we developed another strain which was insensitive to ACTH, produced very little steroid, but had high levels of endogenous c AMP and a growth rate similar to that of the parent Y-1 strain. The current and partially accomplished objectives of this project are to relate cAMP production, the amount of cAMP-receptors, protein kinase activation, cAMP-phosphodiestrase activity, the synthesis of specific labile cytosol proteins, and differences in cell morphology to steroidogenesis and the pattern of cellular proliferation and growth. In order to discover whether a non-neoplastic cell obeys the predictions of our findings, we have introduced several samples of human adrenal cortex to tissue culture. We hope to carry out similar investigations of human adrenocortical cells.